Identification and characterization of a murine model of BCR-ABL1+ acute B-lymphoblastic leukemia with central nervous system metastasis

Abstract

Breakpoint cluster region (BCR)-Abelson murine leukemia (ABL)1+ acute B-lymphoblastic leukemia (B-ALL) is a disease associated with a dismal prognosis and a high incidence of central nervous system (CNS) metastasis. However, BCR-ABL1+ B-ALL with CNS infiltration has not been previously characterized, at least to the best of our knowledge. In the present study, a murine model of BCR-ABL1+ B-ALL with CNS metastasis was established using retroviral transduction. The vast majority of BCR-ABL1+ leukemic cells were found to be immature B cells with a variable proportion of pro-B and pre-B populations. The present results indicated that the BCR-ABL1+ B-leukemic cells expressed high levels integrin subunit alpha 6 (Itga6) and L-selectin adhesion molecules, and have an intrinsic ability to disseminate and accumulate in CNS tissues, predominantly in meninges. On the whole, these results provide an approach for addressing the mechanisms of BCR-ABL1+ B-ALL with CNS metastasis and may guide the development of novel therapeutic strategies.